Small, durable granules, often incorporating two or more ingredients, are desired by users in the aforementioned industries for a myriad of reasons. Products in flowable granular form are durable and easy to store, package and ship without deterioration or disintegration. Also they can be incorporated relatively easily into solid dosage forms for pharmaceutical, biotechnical, neutraceutical, vitamin and process prepared food use by further processing into both capsule and pressed tablet form.
It is well known that durable granules can be made in continuous or batch processes utilizing various prior art methods and process equipment. Examples of such basic prior art methods are disclosed by Tsujimoto U.S. Pat. No. 6,695,989 B 1(Feb. 24, 2004) which describes a fluidized bed granulation chamber and method of operation, and by Key U.S. Pat. No. 5,582,638 B1 (Jun. 24, 2003) which describes a simple mechanical system using a roller and a perforate screen. However, these prior art methods are often highly labor-intensive and time-consuming, and provide an uneconomically low yield of granules with physical sizes within the desired range.
Other prior art methods for producing granules of pharmaceutical materials are described in the following US patents.
Katdare et al. U.S. Pat. No. 6,692,764 B2 (Feb. 17, 2004) discloses (cols. 2–3) a process of wet granulation for compounding pharmaceutical agents to be pressed into tablets. The disclosed process comprises forming a powder blend of active ingredient with diluents, wet grinding the mixture with water to form granules, drying the granules with heated air in a dryer (either fluid bed or tray type), milling the granules to a uniform size, adding and blending a disintegrant, adding and blending a lubricant, and finally compressing the lubricated granule into tablet form. The single milling step takes place only after the product has been dried to its final level of dryness. The process is described as relatively time-consuming, with each of the mixing, granulating drying steps variously taking 20 to 30 minutes, or even 24 hours for tray drying.
Gergely, et al. U.S. Pat. No. 6,645,529 B2 (Nov. 11, 2003) discloses a process of forming “instant” granules (cols. 3–4) in which a carrier material is wetted at least partially before being coated with an active substance, after which additional active substance and liquid are added, followed by drying, final milling, and sieving to desired particle size, with the drying being carried out in a vacuum mixer. The initial mixing step is followed by a single milling step, and then by a final single drying step in a vacuum mixer.
Qui, et al. U.S. Pat. No. 6,419,953 B1 (Jul. 16, 2002) discloses a process (cols. 4–5) involving milling and sieving a bulk drug, mixing it with polymer and excipients in a high shear mixer, and adding liquid to achieve granulation. This is followed by tray drying overnight in a single step. After mixing with lubricant, the dried product is pressed into tablets.
Asgharnejad et al. U.S. Pat. No. 6,123,964 (Sep. 26, 2000) discloses a wet granulation process (cols. 2–4) characterized by mixing powdered active ingredient with a two liquid diluents and a disintegrant in a mixer, wet granulating by adding a solution while mixing, drying the mixed granules in a single step for up to 24 hours, milling the dried granules to a uniform size, adding first a disintegrant and then a lubricant, and finally pressing into tablet form.
Khankari et al. U.S. Pat. No. 6,106,274 B 1(Apr. 24, 2001) describes as “common technique” a method of forming matrix-type particles (cols. 7–8) in which the active substance is spay dried with a solution of polymeric protective material, dried to a solid state in a single step, and then communited (milled) to form the desired particles.
Schobel U.S. Pat. No. 4,687,662 (Aug. 18, 1987) discloses a process for preparing a rapid-dissolving effervescent composition (cols. 7–8) in which a granulation is formed by dissolving a granulating agent in a solvent with the active substance, drying the granulation in a single step, sizing the dried granulation in a single step, and then mixing in an effervescent system to obtain a uniform mixture of granules.